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dc.contributor.authorHeymans, C.
dc.contributor.authorde Lange, I.H.
dc.contributor.authorHütten, M.C.
dc.contributor.authorLenaerts, K.
dc.contributor.authorde Ruijter, N.J.E.
dc.contributor.authorKessels, L.
dc.contributor.authorRademakers, G.
dc.contributor.authorMelotte, V.
dc.contributor.authorBoesmans, W.
dc.contributor.authorSaito, Masatoshi
dc.contributor.authorUsuda, Haruo
dc.contributor.authorStock, S.J.
dc.contributor.authorSpiller, O.B
dc.contributor.authorBeeton, Michael L.
dc.date.accessioned2020-03-27T14:08:56Z
dc.date.available2020-03-27T14:08:56Z
dc.date.issued2020-03-17
dc.identifierhttps://repository.cardiffmet.ac.uk/bitstream/id/47340/fimmu-11-00189%20(1).pdf
dc.identifier.citationHeymans, C. et al. (2020) 'Chronic Intra-Uterine Ureaplasma parvum Infection Induces Injury of the Enteric Nervous System in Ovine Fetuses', Frontiers in Immunology. DOI: 10.3389/fimmu.2020.00189.en_US
dc.identifier.issn1664-3224
dc.identifier.urihttp://hdl.handle.net/10369/10973
dc.descriptionArticle published in Frontiers in Immunology on 17 March 2020, available open access at: https://doi.org/10.3389/fimmu.2020.00189.en_US
dc.description.abstractBackground: Chorioamnionitis, inflammation of the fetal membranes during pregnancy, is often caused by intra-amniotic (IA) infection with single or multiple microbes. Chorioamnionitis can be either acute or chronic, and is associated with adverse postnatal outcomes of the intestine, including necrotizing enterocolitis (NEC). Neonates with NEC have structural and functional damage to the intestinal mucosa and the enteric nervous system (ENS), with loss of enteric neurons and glial cells. Yet, the impact of acute, chronic or repetitive antenatal inflammatory stimuli on the development of the intestinal mucosa and ENS has not been studied. The aim of this study is therefore to investigate the effect of acute, chronic and repetitive microbial exposure on the intestinal mucosa, submucosa and ENS in premature lambs. Materials and Methods: A sheep model of pregnancy was used in which the ileal mucosa, submucosa and ENS were assessed following IA exposure to lipopolysaccharide (LPS) for 2 or 7 days (acute), Ureaplasma parvum (UP) for 42 days (chronic) or repetitive microbial exposure (42 days UP with 2 or 7 days LPS). Results: IA LPS exposure for 7 days or IA UP exposure for 42 days caused intestinal injury and inflammation in the mucosal and submucosal layer of the gut. Repetitive microbial exposure did not further aggravate injury of the terminal ileum. Chronic IA UP exposure caused significant structural ENS alterations characterized by loss of PGP9.5 and S100β immunoreactivity whereas these changes were not found after re-exposure of chronic UP-exposed fetuses to LPS for 2 or 7 days. Conclusion: The in utero loss of PGP9.5 and S100β immunoreactivity following chronic UP exposure corresponds with intestinal changes in neonates with NEC, and may therefore form a novel mechanistic explanation for the association of chorioamnionitis and NEC.en_US
dc.description.sponsorshipThis work was supported by the National Institutes of Health (Bethesda, MD, USA) grant (HD 57869) and the Kinderonderzoekfonds Limburg (TW).en_US
dc.language.isoenen_US
dc.publisherFrontiers Mediaen_US
dc.relation.ispartofseriesFrontiers in Immunology;
dc.titleChronic intra-uterine Ureaplasma parvum infection induces injury of the enteric nervous system in ovine fetusesen_US
dc.typeArticleen_US
dcterms.dateAccepted2020-01-24
rioxxterms.funderCardiff Metropolitan Universityen_US
rioxxterms.identifier.projectCardiff Metropolian (Internal)en_US
rioxxterms.versionAMen_US
rioxxterms.versionofrecordhttps://doi.org/10.3389/fimmu.2020.00189
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/en_US
rioxxterms.licenseref.startdate2020-03-27
rioxxterms.publicationdate2020-03-17
dc.date.refFCD2020-03-27
rioxxterms.funder.project37baf166-7129-4cd4-b6a1-507454d1372een_US


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